Preferred Label : Mutant-selective PI3K-alpha H1047X Inhibitor STX-478;
NCIt synonyms : PIK3CA H1047X Mutant Inhibitor STX-478; Mutant-selective PI3Kalpha H1047X Inhibitor STX-478; PIK3CA H1047X Mutation Inhibitor STX-478;
NCIt definition : An orally bioavailable, brain penetrative, selective inhibitor of the class I phosphatidylinositol-4,5-bisphosphate
3-kinase (PI3K) catalytic subunit alpha (phosphoinositide 3-kinase alpha; PIK3CA;
PI3K p110alpha) mutant H1047X, with potential antineoplastic activity. Upon oral administration,
mutant-selective PI3K-alpha H1047X inhibitor STX-478 selectively targets and allosterically
binds to the PIK3CA mutated form PIK3CA H1047X, thereby preventing the activity of
the H1047X mutant. This prevents PIK3CA H1047X-mediated activation of the PI3K/Akt
(protein kinase B)/mammalian target of rapamycin (mTOR) pathway. This results in both
apoptosis and growth inhibition in PIK3CA H1047X mutant-expressing tumor cells. By
specifically targeting the PIK3CA H1047X mutation, STX-478 may be more efficacious
and less toxic than other PI3K-alpha inhibitors that are not mutant specific. Dysregulation
of the PI3K/Akt/mTOR pathway is often found in solid tumors and results in the promotion
of tumor cell growth, survival, and resistance to chemo- and radio-therapy. PIK3CA,
one of the most frequently mutated oncogenes, encodes the p110-alpha catalytic subunit
of the class I PI3K. STX-478 is able to penetrate the blood-brain-barrier (BBB).;
Molecule name : STX 478; STX-478;
NCI Metathesaurus CUI : CL1906854;
Origin ID : C199491;
concept_is_in_subset
- has_target
